Pre-ischemic Lactate Levels Affect Post-ischemic Recovery in an Isolated Rat Heart Model of Donation After Circulatory Death (DCD)
Copyright © 2021 Arnold, Segiser, Graf, Méndez-Carmona, Sanz, Wyss, Kalbermatter, Keller, Carrel and Longnus..
Introduction: Donation after circulatory death (DCD) could substantially improve donor heart availability. In DCD, the heart is not only exposed to a period of warm ischemia, but also to a damaging pre-ischemic phase. We hypothesized that the DCD-relevant pre-ischemic lactate levels negatively affect the post-ischemic functional and mitochondrial recovery in an isolated rat heart model of DCD. Methods: Isolated, working rat hearts underwent 28.5' of global ischemia and 60' of reperfusion. Prior to ischemia, hearts were perfused with one of three pre-ischemic lactate levels: no lactate (0 Lac), physiologic lactate (0.5 mM; 0.5 Lac), or DCD-relevant lactate (1 mM; 1 Lac). In a fourth group, an inhibitor of the mitochondrial calcium uniporter was added in reperfusion to 1 Lac hearts (1 Lac + Ru360). Results: During reperfusion, left ventricular work (heart rate-developed pressure product) was significantly greater in 0.5 Lac hearts compared to 0 Lac or 1 Lac. In 1 vs. 0.5 Lac hearts, in parallel with a decreased function, cellular and mitochondrial damage was greater, tissue calcium content tended to increase, while oxidative stress damage tended to decrease. The addition of Ru360 to 1 Lac hearts partially abrogated the negative effects of the DCD-relevant pre-ischemic lactate levels (greater post-ischemic left ventricular work and less cytochrome c release in 1 Lac+Ru360 vs. 1 Lac). Conclusion: DCD-relevant levels of pre-ischemic lactate (1 mM) reduce contractile, cellular, and mitochondrial recovery during reperfusion compared to physiologic lactate levels. Inhibition of mitochondrial calcium uptake during early reperfusion improves the post-ischemic recovery of 1 Lac hearts, indicating calcium overload as a potential therapeutic reperfusion target for DCD hearts.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2021 |
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Erschienen: |
2021 |
Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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Enthalten in: |
Frontiers in cardiovascular medicine - 8(2021) vom: 26., Seite 669205 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Arnold, Maria [VerfasserIn] |
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Links: |
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Themen: |
Cardiac ischemia reperfusion injury |
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Anmerkungen: |
Date Revised 02.07.2021 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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doi: |
10.3389/fcvm.2021.669205 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM327420065 |
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520 | |a Introduction: Donation after circulatory death (DCD) could substantially improve donor heart availability. In DCD, the heart is not only exposed to a period of warm ischemia, but also to a damaging pre-ischemic phase. We hypothesized that the DCD-relevant pre-ischemic lactate levels negatively affect the post-ischemic functional and mitochondrial recovery in an isolated rat heart model of DCD. Methods: Isolated, working rat hearts underwent 28.5' of global ischemia and 60' of reperfusion. Prior to ischemia, hearts were perfused with one of three pre-ischemic lactate levels: no lactate (0 Lac), physiologic lactate (0.5 mM; 0.5 Lac), or DCD-relevant lactate (1 mM; 1 Lac). In a fourth group, an inhibitor of the mitochondrial calcium uniporter was added in reperfusion to 1 Lac hearts (1 Lac + Ru360). Results: During reperfusion, left ventricular work (heart rate-developed pressure product) was significantly greater in 0.5 Lac hearts compared to 0 Lac or 1 Lac. In 1 vs. 0.5 Lac hearts, in parallel with a decreased function, cellular and mitochondrial damage was greater, tissue calcium content tended to increase, while oxidative stress damage tended to decrease. The addition of Ru360 to 1 Lac hearts partially abrogated the negative effects of the DCD-relevant pre-ischemic lactate levels (greater post-ischemic left ventricular work and less cytochrome c release in 1 Lac+Ru360 vs. 1 Lac). Conclusion: DCD-relevant levels of pre-ischemic lactate (1 mM) reduce contractile, cellular, and mitochondrial recovery during reperfusion compared to physiologic lactate levels. Inhibition of mitochondrial calcium uptake during early reperfusion improves the post-ischemic recovery of 1 Lac hearts, indicating calcium overload as a potential therapeutic reperfusion target for DCD hearts | ||
650 | 4 | |a Journal Article | |
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650 | 4 | |a heart transplantation | |
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700 | 1 | |a Segiser, Adrian |e verfasserin |4 aut | |
700 | 1 | |a Graf, Selianne |e verfasserin |4 aut | |
700 | 1 | |a Méndez-Carmona, Natalia |e verfasserin |4 aut | |
700 | 1 | |a Sanz, Maria N |e verfasserin |4 aut | |
700 | 1 | |a Wyss, Rahel K |e verfasserin |4 aut | |
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700 | 1 | |a Keller, Nino |e verfasserin |4 aut | |
700 | 1 | |a Carrel, Thierry |e verfasserin |4 aut | |
700 | 1 | |a Longnus, Sarah |e verfasserin |4 aut | |
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